Healthy Aging Lab: Current Research Abstracts

Transcription

1 Healthy Aging Lab: Current Research Abstracts Arsenic Exposure and Women s Health Environmental exposure to inorganic arsenic is an indisputable source of increased risk of several human cancers and chronic diseases such as atherosclerosis and diabetes. Despite a lack of clear understanding of arsenic-induced toxicity, arsenic has multiple adverse effects including an increase in inflammatory markers. There is an intriguing parallel between the chronic inflammatory component recognized to contribute to diseases such as atherosclerosis and diabetes, and the increased risk for other chronic diseases such as sarcopenia (low skeletal muscle mass), high breast cancer risk (higher mammographic density), and osteoporosis (low bone density) in women. The primary aim of this study is to examine whether women who have higher arsenic exposures also have suboptimal body composition, sarcopenia. Secondarily, we will assess whether genes in the arsenic metabolic pathway modify the relationship between arsenic exposure and low skeletal muscle mass. Finally, we will explore the possibility that inflammatory factors are mediators of the relationship between arsenic exposure and sarcopenia. In addition, associations of the urinary arsenic concentration with osteoporosis and breast cancer risk will be examined and potential mechanisms for these associations will be explored using a similar approach in the study of sarcopenia. Participants in this study are women who were enrolled in a cross-sectional study called the Women s Breast and Bone Density Study and conducted by Dr. Zhao Chen. The age range was 41 to 70 and all women were recruited from southern Arizona. Their body composition, breast density and bone density have already been measured and the data are in a de-identified database. In this pilot study, we are planning to analyze 200 archived urine samples to investigate the association between urinary arsenic and metabolite levels and multiple health indicators in women, and how genetic variation might modify those relationships. Selected SNPs in arsenic metabolic pathways (AS3MT, MTHFR) will be analyzed using archived DNA. Selected inflammatory markers (CRP, IL-6sR, IL-1 RA) will be measured using serum specimens. Multiple linear regression analysis with interaction terms will be conducted to investigate associations between exposures and outcomes. Mediating effects for these associations will be assessed by comparing regression models with and without the mediators.

2 Biomarkers and Genetic Factors Related to Sarcopenia in Older Women Low relative skeletal muscle mass (SMM) or sarcopenia significantly contributes to the decline in physical functioning among the elderly. Very little is known about genetic risk factors and their interactions with environmental factors in aging-related SMM loss. There are some indications that inflammatory factors and reduced levels of anabolic hormones are associated with lower muscle mass. These associations need to be confirmed in larger prospective studies and the exact role of each identified biomarker in the development of sarcopenia remains to be investigated. Since physical function impairment and disability are more prevalent in women than in men during their later life, it is especially important to understand the mechanisms of muscle loss and to prevent sarcopenia among older women. The primary objective of this study is to investigate biological mechanisms for sarcopenia by identifying genetic factors and biomarkers that are relevant to low SMM and high rates of SMM loss in older women. We will achieve two specific aims: 1) assess the association of cytokines and hormonal factors with low SMM and the rate of SMM loss; and 2) evaluate the role of genetic variation in catabolic inflammatory cytokines (IL-6, IL-1, TNF-alpha) as well as in anabolic growth factors (IGF1, GH) related to SMM and the rate of SMM loss in ethnicitymatched postmenopausal women. Study participants will come from the Women s Health Initiative Observational Study. All these women have had repeat body composition measurements by using Dual-energy X-ray Absorptiometry (DXA) during the nine-year follow-up. Their SMM will be assessed using a DXA-derived method developed by this research team. Genetic variations in selected catabolic (e.g.il-1, IL6, TNF-a) as well as anabolic (e.g. IGF-1, and GH) factors will be assessed for the entire sample (n = 2800). Analyses of biomarkers, including IL-1a, IL-1b, IL-6, IL-10, TNF-a, TNF-b, Growth Hormone, Insulin, Leptin, C-reactive protein, IL-1ra, IL- 6sR, TNF RII, IGF-1, IGFBP-1 and IGFBP-3, will be conducted among 50% of the participants in this study. Logistic regressions and mixed effect models will be used in the final data analysis. This study is unique and innovative in the study design, selection of bioassays, and the study population. Results of this study may help us to identify high-risk groups for sarcopenia and to develop targeted therapy and preventions to reduce SMM loss and risk of sarcopenia among older women in the US.

3 Anemia and Its Relationship With Sarcopenia, Physical Function, and Mortality Anemia is a common health problem in US older populations; and it increases the risk for disability, decline in physical performance, low muscle strength, and premature death in the elderly. A recent study from NHANES III reported the prevalence of anemia being larger than 10% in the US population over age 65, and the prevalence of anemia varied by ethnicity, suggesting significant health disparities in minorities, especially in the African American population. In this study, a large (N >160,000) multiethnic (non-hispanic white, Hispanic, African American, Native American, Asian/Pacific Islander) cohort from the nationwide Women s Health Initiative (WHI) study will be used to investigate the relationships of aging with anemia epidemiology, pathology and prognosis. Specifically, we will 1) evaluate the frequency of and risk factors for anemia overall and according to race-ethnicity and co-morbidity; 2) determine the association between anemia and risk of death over 10 years of follow-up in the WHI overall and by race-ethnicity; 3) determine associations between anemia and changes in physical function over 9 years of followup in the WHI cohort overall and by race-ethnicity; 4) examine associations of anemia with muscle loss (sarcopenia) among those with baseline and prospective measurements of body composition from dualenergy x-ray absorptiometry; and 5) study the association of anemia with bone loss and risk for osteoporotic fractures in older women. In addition, the frequency of anemia subtypes by morphologic categories and optimal cutoff points of hemoglobin concentrations for anemia in older women will be evaluated. This study will use archived observational and clinical trial data from 40 WHI clinical centers. Additional data entering for blood analysis from existing reports, and data merging (body composition measurements) will be conducted in the WHI DXA cohort from Arizona, Birmingham and Pittsburgh. Multivariate data analyses will be conducted for the specific aims. The WHI provides a unique and invaluable resource for answering the research questions proposed above, as the WHI is the only study in the nation that has prospective co-morbidities and body composition data as well as hemoglobin values in multiethnic groups of older women. This study has a great potential to provide new and critical evidence that is needed for preventing and managing anemia in older women from different health, age and ethnic backgrounds.

4 Longitudinal Changes in Hip Geometry and Skeletal Muscle This study will be conducted among a large multiethnic cohort (N = 11,432) from the nationwide Women's Health Initiative (WHI), which includes an observational study and three clinic trials. The age range of this cohort is between years at the baseline, and it has multiple minority groups: 1583 black, 739 Hispanic and 149 Native American women. The maximal follow-up time of this cohort will be 9 years by Dual-energy x-ray absorptiometry (DXA) is used to measure bone mineral density (BMD) and body composition. The randomized clinical trials and longitudinal nature of the WHI study provide a unique opportunity to investigate: 1) treatment effects of hormone replacement therapy (HRT) and calcium and vitamin D supplementation on hip structural geometry; 2) longitudinal changes in skeletal muscle mass as a factor in hip fragility; and 3) ethnic differences of mean and rates of changes in hip geometry and muscle mass. Special computer software will be used for analyzing hip scans by dual-energy x-ray absorptiometry (DXA). Cross-sectional area, subperiosteal width, estimated endocortical diameter, estimated mean cortical thickness, buckling ratio and section modulus at the femoral neck, at the intertrochanteric and the femoral shaft regions will be assessed. MRI scans will be used as references to calibrate total, appendicular and leg skeletal muscle measurements from DXA subregion analyses. Prevalence rates of sarcopenia (low muscle mass) among each age and ethnic group will be studied. Random Effects Models will be used to analyze the longitudinal data. This proposed study is not funded by the WHI program. Recourses that the WHI will provide include DXA scans, fall and fracture data, and information on covariates. Since the majority of data collection work has been or will be done by the WHI, we will be able to cost-effectively test multiple important scientific hypotheses in this study. The novel approaches in this ancillary study will enhance scientific contributions of the WHI program. The significance of the proposed study is that it may demonstrate the utility of bone structural analysis in addition to bone mass measurements for understanding ethnic differences in fracture risk and/or for assessing the effect of pharmacologic therapy (i.e. HRT) on bone health. Furthermore, if the muscle variables are found to be a strong determinant of bone structure in the proximal femur and the risk of fall, then it may be important to develop interventions to increase muscle mass in this region to prevent hip fracture.

5 Women s Breast and Bone Density Study The primary aim of this study is to examine relationship between the risk of breast cancer and the risk of osteoporosis among non-hispanic and Hispanic white women. Secondly, we will study whether obesity has an effect on mammographic density. In addition, we will explore what factors may alter or modify the relationship between the risk of breast cancer and the risk of osteoporosis. In the proposed cross-sectional study, 150 premenopausal women between the ages of and 150 postmenopausal women between the ages of will be recruited. The participants will be either Non-Hispanic or Hispanic white women who reside in the Tucson metropolitan area. The proportion of Hispanic women will be 50% in both the pre- and the postmenopausal groups. Premenopausal will be defined as women who have had regular menses over the past year. Women have had a hysterectomy or have not had a menstrual cycle for at least one year will be considered postmenopausal if their FSH level is more than 40 miu/1. Participants will be recruited from mammography centers and the local Tucson metropolitan area. Mammographic breast density, bone mineral density, body composition and anthropometric measurements will be assessed on all the participants. The participant's most recent mammogram (within 4 months at the time of bone mineral density test) will be used for the mammographic breast density analysis. Bone density and body composition will be measured by dual-energy x-ray absorptiometry (DXA) with a very low dose of radiation exposure to the subjects. A 12-hour fasting blood (40 ml) will be drawn for FSH analysis on postmenopausal women and stored for hormonal analysis among all participants in the future. An overnight or first morning urine sample will be collected from all the participants for metabolic analysis in the future. Questionnaires will be used to collect information on medical history, family history, dietary intake, physical activity, reproductive history and other lifestyle factors. Statistical analysis will be conducted.

6 Ethnicity, Body Composition, Bone Density, and Breast Cancer Recently two studies reported a strong association between high bone mass and increased risk of breast cancer. This result raised new questions in decision-making for HRT and suggests a potential use of bone mass as an indicator of lifetime estrogen for assessing the risk of breast cancer. Additional studies should be conducted in different ethnic groups, because there significant ethnic variation in frequencies, distributions and severity levels of both osteoporosis and breast cancer. Given the fact that the bone mineral density (BMD) is higher, but the rate of breast cancer in lower in Hispanic older women compared with Anglo women, the Hispanic postmenopausal women will be a very interesting model to further evaluate this interrelationship between breast cancer and bone mass. To date, most of our knowledge of risk factor of osteoporosis and breast cancer are mainly based on results from Anglo women. It is critical to examine those risk factors in the Hispanic women population in order to form specific prevention strategies for this population. The women s Health Initiative (WHI) provided a unique opportunity to undertake nested casecontrol studies (NCCS) to further examine these issues in different ethnic groups. The number of Hispanic women in the WHI BMD study cohorts is small (Nexpected = 800) and the breast cancer rate is lower in Hispanic women compared with Anglo. Therefore within the WHI there will not be a sufficient number of breast cancer cases to form a NCCS in Hispanic women. The proposed study is a case control research design. The controls will be chosen from Hispanic participants of the Arizona WHI observation study group. No additional data will be collected from the controls. The cases (N=140). Will be newly diagnosed Hispanic and White postmenopausal breast cancer patients in Arizona (obtained through collaborative oncologists and surgeons). The measurement will include anthropometry, body composition, BMD, peripheral white blood cells and WHI questionnaires. The interrelationship between BMD and breast cancer will be evaluated using logistic regression analysis.

The Longest Title in the Meeting Steven R. Cummings, MD, FACP S.F. Coordinating Center Financial support from several companies that make treatments for osteopenia and osteoporosis "What is critical for

New study finds 1 in 7 young Canadian adults vitamin C deficient The following is an excerpt by Ahmed El-Sohemy, PhD, a lead researcher in the newly published Canadian study examining ascorbic acid deficiency

Cystic fibrosis and bone health Factsheet March 2013 Cystic fibrosis and bone health Introduction As we get older our bones become thinner and weaker, and may become more susceptible to fracture. However

Healthy Bones at Every Age Page ( 1 ) Bone health is important at every age and stage of life. The skeleton is our body s storage bank for calcium a mineral that is necessary for our bodies to function.

MAKING SENSE OF THE NUMBERS Gary W. Swenson, MD GWS is a partner at Radiologists of North Iowa, which jointly owns with Mercy Medical Center North Iowa, the Forest Park Imaging Center, a provider of DXA

How do inflammatory markers in postmenopausal women change after a year long high versus moderate exercise intervention? Photo credit: Canadian Cancer Society Acknowledgements Co authors: Rachel O Reilly,

How to Use the Research Design Algorithm Below is a diamond by diamond guide for using the Research Design Algorithm developed by the Academy of Nutrition and Dietetics, 2010. Included are Tips on what

What You Need to Know for Better Bone Health A quick lesson about bones: Why healthy bones matter The healthier your bones The more active you can be Bone health has a major effect on your quality of life

16. ARTHRITIS, OSTEOPOROSIS, AND CHRONIC BACK CONDITIONS Goal Reduce the impact of several major musculoskeletal conditions by reducing the occurrence, impairment, functional limitations, and limitation

Endocrine issues in FA SUSAN R. ROSE CINCINNATI CHILDREN S HOSPITAL MEDICAL CENTER 80% of children and adults with FA have an endocrine abnormality Endocrine cells make a hormone (message) Carried in bloodstream

Recommendations for Care of the Osteoporotic Fracture Patient to Reduce the Risk of Future Fracture Developed by the World Orthopedic Osteoporosis Organization (WOOO) Olof Johnell 1, John Kaufman 2, Steven

PROTOCOL FOR PATIENTS WITH ABNORMAL LAB AND X-RAY VALUES Patients newly diagnosed as osteopenic or osteoporotic on a radiology report or patients receiving abnormal lab values on the following lab tests

New Guidelines for the Prevention and Treatment of Osteoporosis E. Michael Lewiecki, MD, and Nelson B. Watts, MD Abstract: The World Health Organization Fracture Risk Assessment Tool (FRAX ) and the National

Orthopaedic Issues in Adults with CP: If I Knew Then, What I Know Now Laura L. Tosi, MD Director, Bone Health Program Children s National Medical Center Washington, DC Epidemiology 87-93% of children born

What is Bone Densitometry? Every day, physicians use radiography, or x-rays, to view and evaluate bone fractures and other injuries of the musculoskeletal system. However, a plain x-ray test is not the

The National Center for Health Statistics' Linked Data Files: Resources for Research and Policy Eric A. Miller National Center for Health Statistics NCHS Record Linkage Program Links survey data with data

Menopause and Hormone Therapy: Dr Zeelha Abdool Introduction: Menopause is defined as the permanent cessation of menstruation (1 year after your last period), and is therefore a retrospective diagnosis.

11 BMD: Interpretation and Normal Ranges Introduction Bone mineral density measurements are frequently used in clinical practice to assess fracture risk. The utility of these measurements depends on making

What is osteoporosis? What is osteopenia? Osteoporosis is a problem in which bones are less dense and more fragile and thus at greater risk for fracture, even with a small amount of trauma. This disease

Diabetes and Obesity in Children Janie Berquist, RN, BSN, MPH, CDE Children s Mercy Hospitals and Clinics Kansas City, MO Diabetes and Obesity in Children What is Diabetes? How are Diabetes and Obesity

Scan for mobile link. Bone Densitometry Bone densitometry, also called dual-energy x-ray absorptiometry or DEXA, uses a very small dose of ionizing radiation to produce pictures of the inside of the body

Goals of This Course Be able to understand a study design (very basic concept) Be able to understand statistical concepts in a medical paper Be able to perform a data analysis Understanding: PECO study

FastTest You ve read the book...... now test yourself To ensure you have learned the key points that will improve your patient care, read the authors questions below. Please refer back to relevant sections

Q.1 If you were diagnosed with cancer today, what would your chances of survival be? Ongoing medical research from the last two decades has seen the cancer survival rate increase by more than 40%. However

American Medical Women s Association Position Paper on Principals of Breast Cancer Screening Breast cancer affects one woman in eight in the United States and is the most common cancer diagnosed in women

CONTENT SPECIFICATIONS The Bone Densitometry Examination The purpose of The American Registry of Radiologic Technologist (ARRT ) Bone Densitometry Examination is to assess the knowledge and cognitive skills

Osteoporosis Assessment Using DXA and Instant Vertebral Assessment Working Together For A Healthier Community Osteoporosis The Silent Thief The Facts About Osteoporosis 1 in 2 women will develop osteoporosis

Cystic fibrosis and bone health Factsheet August 2015 Cystic fibrosis and bone health Introduction As we get older our bones become thinner and weaker, and may become more susceptible to fracture. However,

The Menopause Definition The menopause in it s literal definition means the end of monthly cycles ; from the Greek word paussis (cessation) and the root men- (month) 1. This definition, however, refers

Boning Up On Osteoporosis Nicholas J. Avallone,, M.D. Orthopedic Surgeon Sports Medicine Specialist Conflicts of Interest I have no relationships with any company listed in this talk. Resources National

European Medicines Agency London, 16 November 2006 Doc. Ref. CPMP/EWP/552/95 Rev. 2 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) GUIDELINE ON THE EVALUATION OF MEDICINAL PRODUCTS IN THE TREATMENT

RAD216 ADVANCED IMAGING MODALITIES BONE DENSITOMETRY INTRODUCTION Over the last 50+ years, medical imaging has been at the forefront in the development of ways to better diagnose bone mineral loss. This

When you have osteoporosis, your bones become weak and are more likely to break (fracture). You can have osteoporosis without any symptoms. Because it can be prevented and treated, an early diagnosis is

Clinical Practice Guideline for Osteoporosis Screening and Treatment Osteoporosis is a condition of decreased bone mass, leading to bone fragility and an increased susceptibility to fractures. While osteoporosis

OSTEOPOROSIS IS A DISEASE OF THE BONES, WHICH LEADS TO AN INCREASED RISK OF FRACTURE. IN OSTEOPOROSIS, THE DENSITY AND QUALITY OF BONE ARE REDUCED. THE LOSS OF BONE OCCURS SILENTLY AND PROGRESSIVELY. Osteoporosis

Web Quest Abstract Students explore the Using Family History to Improve Your Health module on the Genetic Science Learning Center website to complete a web quest. Learning Objectives Chronic diseases such

Bio Impedance Analysis Find out what you re made of! These days we love technology and what better way to track your health than via a state of the art electronic set of scales. Wellnation Clinics at Endeavour

X-Plain Vertebral Compression Fractures Reference Summary Introduction Back pain caused by a vertebral compression fracture, or VCF, is a common condition that affects thousands of people every year. A

Drug treatments to protect your bones This information is an extract from the booklet, Bone health. You may find the full booklet helpful. We can send you a copy free see page 5. Contents Bisphosphonates

THE ROLE OF TUMOUR NECROSIS FACTOR ALPHA (TNFa) IN OBESITY Alison Mary Morris, B.Sc (Hons) A thesis submitted to Adelaide University for the degree of Doctor of Philosophy Department of Physiology Adelaide

Prostate Cancer Screening A Decision Guide for African Americans This booklet was developed by the U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). Published

THINGS TO BE AWARE OF ABOUT PROSTATE AND LUNG CANCER Lawrence Lackey Jr., M.D. Internal Medicine 6001 W. Outer Dr. Ste 114 WHAT IS CANCER? The body is made up of hundreds of millions of living cells. Normal

Scans and tests and osteoporosis What is osteoporosis? Osteoporosis occurs when the struts which make up the mesh-like structure within bones become thin causing them to become fragile and break easily,

D. Vitamin D. Two main forms; vitamin D2 and D3 H H D3 - Cholecalciferol D2 - Ergocalciferol Technically, vitamin D is not a vitamin. It is the name given to a group of fat-soluble prohormones (substances

s Preventive Care Services Manage Your Chronic Kidney Disease (CKD stages 3-4) with Diet What do the kidneys do? Your kidneys have important jobs to do in your body. Two of the kidneys most important jobs

5.7 Recommendations for preventing osteoporosis 5.7.1 Background Osteoporosis is a disease affecting many millions of people around the world. It is characterized by low bone mass and micro-architectural

Randomized trials versus observational studies The case of postmenopausal hormone therapy and heart disease Miguel Hernán Harvard School of Public Health www.hsph.harvard.edu/causal Joint work with James